Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).Aim
Patients and Methods
We sought to determine if a durable bilayer implant composed of trabecular metal with autologous periosteum on top would be suitable to reconstitute large osteochondral defects. This design would allow for secure implant fixation, subsequent integration and remodeling. Adult sheep were randomly assigned to one of three groups (n = 8/group): 1. trabecular metal/periosteal graft (TMPG), 2. trabecular metal (TM), 3. empty defect (ED). Cartilage and bone healing were assessed macroscopically, biochemically (type II collagen, sulfated glycosaminoglycan (sGAG) and double-stranded DNA (dsDNA) content) and histologically.Objectives
Materials and Methods
The aim of this study was to investigate the changes in femoral
trochlear morphology following surgical correction of recurrent
patellar dislocation associated with trochlear dysplasia in children. A total of 23 patients with a mean age of 9.6 years (7 to 11)
were included All had bilateral recurrent patellar dislocation associated
with femoral trochlear dysplasia. The knee with traumatic dislocation
at the time of presentation or that had dislocated most frequently
was treated with medial patellar retinacular plasty (Group S). The
contralateral knee served as a control and was treated conservatively
(Group C). All patients were treated between October 2008 and August
2013. The mean follow-up was 48.7 months (43 to 56). Axial CT scans
were undertaken in all patients to assess the trochlear morphological
characteristics on a particular axial image which was established
at the point with the greatest epicondylar width based on measurements
preoperatively and at the final follow-up.Aims
Patients and Methods
Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA. This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.Objectives
Methods
The aim of this study was to identify key pathological genes in osteoarthritis (OA). We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis.Objectives
Methods
Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage.Objectives
Methods
Medial unicompartmental knee arthroplasty (UKA) is associated
with successful outcomes in carefully selected patient cohorts.
We hypothesised that severity and location of patellofemoral cartilage
lesions significantly influences functional outcome after Oxford
medial compartmental knee arthroplasty. We reviewed 100 consecutive UKAs at minimum eight-year follow-up
(96 to 132). A single surgeon performed all procedures. Patients
were selected based on clinical and plain radiographic assessment.
All patients had end-stage medial compartment osteoarthritis (OA)
with sparing of the lateral compartment and intact anterior cruciate ligaments.
None of the patients had end-stage patellofemoral OA, but patients
with anterior knee pain or partial thickness chondral loss were
not excluded. There were 57 male and 43 female patients. The mean
age at surgery was 69 years (41 to 82). At surgery the joint was
carefully inspected for patellofemoral chondral loss and this was documented
based on severity of cartilage loss (0 to 4 Outerbridge grading)
and topographic location (medial, lateral, central, and superior
or inferior). Functional scores collected included Oxford Knee Score
(OKS), patient satisfaction scale and University College Hospital
(UCH) knee score. Intraclass correlation was used to compare chondral
damage to outcomes.Aims
Patients and Methods
Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from
This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR).Objectives
Methods
The aim of this study was to investigate the effect of granulocyte-colony stimulating factor (G-CSF) on mesenchymal stem cell (MSC) proliferation MSCs from rabbits were cultured in a control medium and medium with G-CSF (low-dose: 4 μg, high-dose: 40 μg). At one, three, and five days after culturing, cells were counted. Differential potential of cultured cells were examined by stimulating them with a osteogenic, adipogenic and chondrogenic medium. A total of 30 rabbits were divided into three groups. The low-dose group (n = 10) received 10 μg/kg of G-CSF daily, the high-dose group (n = 10) received 50 μg/kg daily by subcutaneous injection for three days prior to creating cartilage defects. The control group (n = 10) was administered saline for three days. At 48 hours after the first injection, a 5.2 mm diameter cylindrical osteochondral defect was created in the femoral trochlea. At four and 12 weeks post-operatively, repaired tissue was evaluated macroscopically and microscopically.Objectives
Methods
Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O.Objectives
Methods
Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (Objectives
Methods
This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA). Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2-△△CT method. All data were processed using SPSS software.Objectives
Methods
The major problem with repair of an articular cartilage injury
is the extensive difference in the structure and function of regenerated,
compared with normal cartilage. Our work investigates the feasibility
of repairing articular osteochondral defects in the canine knee
joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate
(ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells
(BMSCs) and assesses its biological compatibility. The bone–cartilage scaffold was prepared as a laminated composite,
using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer
of polylactic acid–hydroxyacetic acid as the bony scaffold, and
sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous
scaffold. Ten-to 12-month-old hybrid canines were randomly divided
into an experimental group and a control group. BMSCs were obtained
from the iliac crest of each animal, and only those of the third
generation were used in experiments. An articular osteochondral
defect was created in the right knee of dogs in both groups. Those
in the experimental group were treated by implanting the composites
consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs.
Those in the control group were left untreated.Objectives
Methods
The treatment of osteochondral lesions is of
great interest to orthopaedic surgeons because most lesions do not heal
spontaneously. We present the short-term clinical outcome and MRI
findings of a cell-free scaffold used for the treatment of these
lesions in the knee. A total of 38 patients were prospectively evaluated
clinically for two years following treatment with an osteochondral
nanostructured biomimetic scaffold. There were 23 men and 15 women; the
mean age of the patients was 30.5 years (15 to 64). Clinical outcome
was assessed using the Knee Injury and Osteoarthritis Outcome Score
(KOOS), the Tegner activity scale and a Visual Analgue scale for
pain. MRI data were analysed based on the Magnetic Resonance Observation
of Cartilage Repair Tissue (MOCART) scoring system at three, 12
and 24 months post-operatively. There was a continuous significant
clinical improvement after surgery. In two patients, the scaffold
treatment failed (5.3%) There was a statistically significant improvement
in the MOCART precentage scores. The repair tissue filled most of
the defect sufficiently. We found subchondral laminar changes in all
patients. Intralesional osteophytes were found in two patients (5.3%).
We conclude that this one-step scaffold-based technique can be used
for osteochondral repair. The surgical technique is straightforward,
and the clinical results are promising. The MRI aspects of the repair
tissue continue to evolve during the first two years after surgery.
However, the subchondral laminar and bone changes are a concern. Cite this article:
We studied whether the presence of lateral osteophytes
on plain radiographs was a predictor for the quality of cartilage
in the lateral compartment of patients with varus osteoarthritic
of the knee (Kellgren and Lawrence grade 2 to 3). The baseline MRIs of 344 patients from the Osteoarthritis Initiative
(OAI) who had varus osteoarthritis (OA) of the knee on hip-knee-ankle
radiographs were reviewed. Patients were categorised using the Osteoarthritis
Research Society International (OARSI) osteophyte grading system
into 174 patients with grade 0 (no osteophytes), 128 grade 1 (mild
osteophytes), 28 grade 2 (moderate osteophytes) and 14 grade 3 (severe
osteophytes) in the lateral compartment (tibia). All patients had
Kellgren and Lawrence grade 2 or 3 arthritis of the medial compartment.
The thickness and volume of the lateral cartilage and the percentage
of full-thickness cartilage defects in the lateral compartment was
analysed. There was no difference in the cartilage thickness or cartilage
volume between knees with osteophyte grades 0 to 3. The percentage
of full-thickness cartilage defects on the tibial side increased
from <
2% for grade 0 and 1 to 10% for grade 3. The lateral compartment cartilage volume and thickness is not
influenced by the presence of lateral compartment osteophytes in
patients with varus OA of the knee. Large lateral compartment osteophytes
(grade 3) increase the likelihood of full-thickness cartilage defects
in the lateral compartment. Cite this article:
Radiostereometric analysis (RSA) allows an extremely accurate
measurement of early micromotion of components following arthroplasty. In this study, RSA was used to measure the migration of 11 partially
cemented fluted pegged glenoid components in patients with osteoarthritis
who underwent total shoulder arthroplasty using an improved surgical
technique (seven men, four women, mean age 68). Patients were evaluated
clinically using the American Shoulder and Elbow Surgeons (ASES)
and Constant-Murley scores and by CT scans two years post-operatively. Aims
Patients and Methods
